• Performance of FASTPlaqueTB and a modified protocol in a high HIV prevalence community in South Africa.

      Trollip, A P; Albert, H; Mole, R; Marshall, T; van Cutsem, G; Coetzee, D; Biotec Laboratories South Africa Ltd, Cape Town, South Africa. andre.trollip@bioteclabs.co.za (2009-06)
      Modifications in the FASTPlaqueTB test protocol have resulted in an increase in the analytical limits of detection. This study investigated whether the performance of a modified prototype was able to increase the detection of smear-negative, culture-positive sputum samples as compared to the first generation FASTPlaqueTB test. Modifications to the FASTPlaqueTB did result in increased detection of smear-negative samples, but this was associated with a decrease in the specificity of the test. Before the FASTPlaqueTB can be considered as a viable replacement for smear microscopy and culture for the identification of tuberculosis, further work is required to resolve the performance issues identified in this study.
    • Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial).

      Borand, Laurence; Madec, Yoann; Laureillard, Didier; Chou, Monidarin; Marcy, Olivier; Pheng, Phearavin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeun; et al. (Public Library of Science, 2014)
      To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.
    • Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi.

      Nicholas, S; Poulet, E; Wolters, L; Wapling, J; Rakesh, A; Amoros, I; Szumilin, E; Gueguen, M; Schramm, B (John Wiley & Sons, 2019-08-01)
      INTRODUCTION: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi. METHODS: We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. RESULTS AND DISCUSSION: Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed. CONCLUSIONS: Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.
    • Pooled HIV-1 Viral Load Testing Using Dried Blood Spots to Reduce the Cost of Monitoring Antiretroviral Treatment in a Resource-Limited Setting

      Pannus, Pieter; Fajardo, Emmanuel; Metcalf, Carol; Coulborn, Rebecca M; Durán, Laura T; Bygrave, Helen; Ellman, Tom; Garone, Daniela; Murowa, Michael; Mwenda, Reuben; et al. (Lippincott Williams & Wilkins, 2013-10-01)
      : Rollout of routine HIV-1 viral load monitoring is hampered by high costs and logistical difficulties associated with sample collection and transport. New strategies are needed to overcome these constraints. Dried blood spots from finger pricks have been shown to be more practical than the use of plasma specimens, and pooling strategies using plasma specimens have been demonstrated to be an efficient method to reduce costs. This study found that combination of finger-prick dried blood spots and a pooling strategy is a feasible and efficient option to reduce costs, while maintaining accuracy in the context of a district hospital in Malawi.
    • Population Differences in Death Rates in HIV-Positive Patients with Tuberculosis.

      Ciglenecki, I; Glynn, J R; Mwinga, A; Ngwira, B; Zumla, A; Fine, P E M; Nunn, A; Médecins Sans Frontières, Geneva, Switzerland. iza_ciglenecki@yahoo.com (International Union Against TB and Lung Disease, 2007-10)
      SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality.
    • Population-level HIV incidence estimates using a combination of synthetic cohort and recency biomarker approaches in KwaZulu-Natal, South Africa

      Grebe, E; Welte, A; Johnson, LF; van Cutsem, G; Puren, A; Ellman, T; Etard, JF; Huerga, H (Public Library of Science, 2018-09-13)
      There is a notable absence of consensus on how to generate estimates of population-level incidence. Incidence is a considerably more sensitive indicator of epidemiological trends than prevalence, but is harder to estimate. We used a novel hybrid method to estimate HIV incidence by age and sex in a rural district of KwaZulu-Natal, South Africa.
    • Positive spill-over effects of ART scale up on wider health systems development: evidence from Ethiopia and Malawi

      Rasschaert, Freya; Pirard, Marjan; Philips, Mit P; Atun, Rifat; Wouters, Edwin; Assefa, Yibeltal; Criel, Bart; Schouten, Erik J; Van Damme, Wim (2011)
    • Potential Impact of Multiple Interventions on HIV Incidence in a Hyperendemic Region in Western Kenya: a Modelling Study

      Blaizot, S; Maman, D; Riche, B; Mukui, I; Kirubi, B; Ecochard, R; Etard, JF (BioMed Central, 2016-04-29)
      Multiple prevention interventions, including early antiretroviral therapy initiation, may reduce HIV incidence in hyperendemic settings. Our aim was to predict the short-term impact of various single and combined interventions on HIV spreading in the adult population of Ndhiwa subcounty (Nyanza Province, Kenya).
    • Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

      Bedell, RA; van Lettow, M; Meaney, C; Corbett, EL; Chan, AK; Heyderman, RS; Anderson, ST; Akesson, A; Kumwenda, M; Zachariah, R; et al. (Wiley-Blackwell, 2018-01-01)
      BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). METHODS: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. RESULTS: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. CONCLUSION: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.
    • Predictors of Raised Viral Load during Antiretroviral Therapy in Patients with and without Prior Antiretroviral Use: A Cross-Sectional Study

      Greig, Jane E.; du Cros, Philipp A; Mills, Clair; Ugwoeruchukwu, Wilfred; Etsetowaghan, Andrew; Grillo, Adetola; Tayo-Adetoro, Adetoro; Omiyale, Kunle; Spelman, Tim; O'Brien, Daniel P.; et al. (PLoS, 2013-08-14)
      In Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with ("experienced") and without ("naïve") prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry.
    • Preferred antiretroviral drugs for the next decade of scale up

      Andrieux-Meyer, Isabelle; Calmy, Alexandra; Cahn, Pedro; Clayden, Polly; Raguin, Gilles; Katlama, Christine; Vitoria, Marco; Levin, Andrew; Lynch, Sharonann; Goemaere, Eric; et al. (2012-09-18)
      Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.
    • Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

      Micol, Romain; Buchy, Philippe; Guerrier, Gilles; Duong, Veasna; Ferradini, Laurent; Dousset, Jean-Philippe; Guerin, Philippe J; Balkan, Suna; Galimand, Julie; Chanroeun, Hak; et al. (2009-08-01)
      BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality.
    • Preventing HIV-1: lessons from Mwanza and Rakai.

      Matthys, F; Boelaert, M (Elsevier, 1999-05-01)
    • The prevention of mother-to-child HIV transmission programme and infant feeding practices.

      Hilderbrand, K; Goemaere, E; Coetzee, D; Infectious Diseases and HIV/AIDS Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town. (2003-10)
      Since the first cases of HIV transmission through breast-feeding were documented, a fierce debate has raged on appropriate guidelines for infant feeding in resource-poor settings. A major problem is determining when it is safe and feasible to formula-feed, as breast-milk protects against other diseases. A cross-sectional survey of 113 women attending the programme for the prevention of mother-to-child transmission in Khayelitsha, Cape Town, was conducted. Over 95% of women on the programme formula-fed their infants and did not breast-feed at all. Seventy per cent of women said that their infant had never had diarrhoea, and only 3% of children had had two episodes of diarrhoea. Focus groups identified the main reasons for not breast-feeding given by women to their families and those around them. Formula feeding is safe and feasible in an urban environment where sufficient potable water is available.
    • Prevention of mother-to-child transmission of HIV and the health-related Millennium Development Goals: time for a public health approach.

      Schouten, Erik J; Jahn, Andreas; Midiani, Dalitso; Makombe, Simon D; Mnthambala, Austin; Chirwa, Zengani; Harries, Anthony D; van Oosterhout, Joep J; Meguid, Tarek; Ben-Smith, Anne; et al. (2011-07-16)
    • Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings

      Spaar, A; Graber, C; Dabis, F; Coutsoudis, A; Bachmann, L; McIntyre, J; Schechter, M; Prozesky, H W; Tuboi, S; Dickinson, D; et al. (2010-05-13)
      Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.
    • Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.

      Boulle, A; Teck, R; Lukhele, N; Rusch, B; Telnov, A; Mabhena, E; Pasipamire, L; Ciglenecki, I; Schomaker, M; Kerschberger, B (John Wiley & Sons, 2019-04-01)
      To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland). This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates. Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes.
    • Progress towards the UNAIDS 90-90-90 goals by age and gender in a rural area of KwaZulu-Natal, South Africa: a household-based community cross-sectional survey

      Huerga, H; Van Cutsem, G; Ben Farhat, J; Puren, A; Bouhenia, M; Wiesner, L; Dlamini, L; Maman, D; Ellman, T; Etard, JF (BioMed Central, 2018-03-02)
      The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed an ambitious strategy to end the AIDS epidemic. After eight years of antiretroviral therapy (ART) program we assessed progress towards the UNAIDS 90-90-90 targets in Mbongolwane and Eshowe, KwaZulu-Natal, South Africa.
    • Promoting adherence to antiretroviral therapy: the experience from a primary care setting in Khayelitsha, South Africa.

      Coetzee, D; Boulle, A; Hildebrand, K; Asselman, V; Van Cutsem, G; Goemaere, E; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. dcoetzee@phfm.uct.ac.za (2004-06)
      OBJECTIVE: To describe the approach used to promote adherence to antiretroviral therapy (ART) and to present the outcomes in the first primary care public sector ART project in South Africa. DESIGN: The study is a prospective open cohort, including all adult patients naive to previous ART who received antiretroviral treatment in Khayelitsha, from May 2001 to the end of 2002. Patients were followed until their most recent visit before 31 July 2003. METHODS: Plasma viral load was determined at 3, 6, 12, 18 and 24 months after ART was initiated, and CD4 cell counts 6-monthly. Kaplan-Meier estimates were determined for the cumulative proportions of patients surviving, and patients with viral load suppression and viral rebound. RESULTS: A total of 287 patients were initiated on triple therapy. The probability of survival was 86.3% at 24 months. The median CD4 cell count gain was 288 cells/microliters at 24 months. Viral load was less than 400 copies/ml in 89.2, 84.2 and 69.7% of patients at 6, 12 and 24 months, respectively. The cumulative probability of viral rebound (two consecutive HIV-RNA measurements above 400 copies/ml) after achieving an HIV-RNA measurement below 400 copies/ml was 13.2% at 18 months. CONCLUSION: The study shows that, with a standard approach to patient preparation and strategies to enhance adherence, a cohort of patients on ART can be retained in a resource-limited setting in a developing country. A high proportion of patients achieved suppression of viral replication. The subsequent probability of viral rebound was low.
    • Promoting long term adherence to Antiretroviral Treatment

      Mills, Edward J; Lester, Richard; Ford, Nathan (2012-06-28)